A double-blind, placebo-controlled investigation of the efficacy of modafinil for sustaining the alertness and performance of aviators: a helicopter simulator study

Rationale: In 1998, the FDA approved modafinil for treating excessive dayti me sleepiness in narcoleptics, and this has raised questions about the appr opriateness of this compound for enhancing alertness in sleep-deprived cont rols. This study explored the efficacy of modafinil for maintaining the per formance of volunteers required to accomplish highly demanding tasks despit e sleep loss. Objective: The principal objective was to determine whether p rophylactic doses of modafinil would attenuate decrements in aviator perfor mance and arousal throughout 2 days and 1 night without sleep. Methods: Six pilots were exposed to two 40-h periods of continuous wakefulness. In one, three 200-mg doses of modafinil were given and in the other, matching plac ebos were administered. Helicopter simulator flights, resting EEGs, and Pro file of Mood States (POMS) questionnaires were evaluated. Results: Modafini l attenuated sleep deprivation effects on four of six flight maneuvers, red uced slow-wave EEG activity, and lessened self-reported problems with mood and alertness in comparison to placebo. The most noticeable benefits occurr ed between 0330 and 1130 hours, when the combined impact of sleep loss and the circadian trough was most severe. The most frequently observed drug sid e effects were vertigo, nausea, and dizziness. These could have been relate d to: 1) the motion-based testing, 2) the use of a simulator rather than an actual aircraft (i.e., "simulator sick ness"), and/or 3) the administratio n of more than 400 mg modafinil. Conclusions: Modafinil is a promising coun termeasure for sleep loss in normals: however, additional studies aimed at reducing side effects are needed before it should be used in aviators.